USP38-NF33_C71_無(wú)菌檢查法-中英對(duì)照

1、USP38 NF33<71> STERILITY TESTS<71>無(wú)菌檢查法Portions of this general chapter have been harmonized with the corresponding texts of the European Pharmacopeia and/or the Japanese Pharmacopeia. Those portions that are not harmonized are marked with symbols ( ) to specify this fact.本檢查法已與歐洲藥典和日本藥局

2、方對(duì)應(yīng)部分進(jìn)行了協(xié)調(diào)，不一致的部分用符號(hào)()標(biāo)注。These Pharmacopeial procedures are not by themselves designed to ensure that a batch of product is sterile or has been sterilized. This is accomplished primarily by validation of the sterilization process or of the aseptic processing procedures.按藥典規(guī)定的無(wú)菌檢驗(yàn)本身并不能確保一批產(chǎn)品無(wú)菌或已經(jīng)滅菌，產(chǎn)

3、品的無(wú)菌性主要通過(guò)對(duì)滅菌工藝或者無(wú)菌保障程序的驗(yàn)證來(lái)完成。The test is applied to substances, preparations, or articles which, according to the Pharmacopeia, are required to be sterile. However, a satisfactory result only indicates that no contaminating microorganism has been found in the sample examined under the conditions of

4、the test.無(wú)菌檢查法系用于檢查藥典要求無(wú)菌的藥物、制劑產(chǎn)品和其他物品是否無(wú)菌的一種方法。若供試品符合無(wú)菌檢查法的規(guī)定，僅表明供試品在該檢驗(yàn)條件下未發(fā)現(xiàn)微生物污染。PRECAUTIONS AGAINST MICROBIAL CONTAMINATION預(yù)防微生物污染The test for sterility is carried out under aseptic conditions. In order to achieve such conditions, the test environment has to be adapted to the way in which the s

5、terility test is performed. The precautions taken to avoid contamination are such that they do not affect any microorganisms that are to be revealed in the test. The working conditions in which the tests are performed are monitored regularly by appropriate sampling of the working area and by carryin

6、g out appropriate controls.無(wú)菌檢查應(yīng)在無(wú)菌條件下進(jìn)行，為了達(dá)到該條件，檢測(cè)環(huán)境應(yīng)符合無(wú)菌檢查的規(guī)定。防止污染的措施不得影響供試品中微生物的檢出。檢測(cè)環(huán)境應(yīng)定期抽樣監(jiān)測(cè)并進(jìn)行適當(dāng)?shù)目刂?。CULTURE MEDIA AND INCUBATION TEMPERATURES培養(yǎng)基和培養(yǎng)溫度Media for the test may be prepared as described below or equivalent commercial media may be used provided that they comply with the requirements

7、of the Growth Promotion Test of Aerobes, Anaerobes, and Fungi.無(wú)菌檢查需制備下表所述培養(yǎng)基，或者是能夠符合需氣菌、厭氧菌、真菌促生長(zhǎng)試驗(yàn)要求的同等的商用培養(yǎng)基。The following culture media have been found to be suitable for the test for sterility. Fluid Thioglycollate Medium is primarily intended for the culture of anaerobic bacteria. However, it w

8、ill also detect aerobic bacteria. SoybeanCasein Digest Medium is suitable for the culture of bothfungi and aerobic bacteria.以下培養(yǎng)基已經(jīng)被證實(shí)適合用于無(wú)菌檢查，硫乙醇酸鹽流體培養(yǎng)基主要用于厭氧菌的培養(yǎng)，但其也可用于需氣菌培養(yǎng)。大豆-酪胨培養(yǎng)基適合于培養(yǎng)真菌和需氣菌。硫乙醇酸鹽流體培養(yǎng)基L-胱氨酸0.5g氯化鈉2.5g水合葡萄糖/無(wú)水葡萄糖5.5/5.0g瓊脂0.75g酵母提取物（水溶的）5.0g胰酶消化酪蛋白胨15.0g硫乙醇酸鈉0.5g或硫乙醇酸0.3 mL新配制的刃

9、天青水溶液（1:1000）1.0mL純化水1000 mLpH after sterilization: 7.1±0.2.滅菌后pH：7.1±0.2。Mix the L-cystine, agar, sodium chloride, dextrose, yeast extract, and pancreatic digest of casein with the purified water, and heat until solution is effected. Dissolve the sodium thioglycollate or thioglycolic acid

10、 in the solution and, if necessary, add 1 N sodium hydroxide so that, after sterilization, the solution will have a pH of 7.1 ± 0.2. If filtration is necessary, heat the solutionagain without boiling, and filter while hot through moistened filter paper. Add the resazurin sodium solution, mix, a

11、nd place the medium in suitable vessels that provide a ratio of surface to depth of medium such that not more than the upper half of the medium has undergone a color change indicative of oxygen uptake at the end of the incubation period. Sterilize using a validated process.If the medium is stored, s

12、tore at a temperature between 2 and 25 in a sterile, airtight container. If more than the upper one-third of the medium has acquired a pink color, the medium may be restored once by heating the containers in a water-bath or in free-flowing steam until the pink color disappears and by cooling quickly

13、, taking care to prevent the introduction of nonsterile air into the container. Do not use the medium for a longer storage period than has been validated.將L-胱氨酸、氯化鈉、葡萄糖、酵母提取物、酪蛋白胰酶消化物與純化水混合，并加熱至溶解。將硫乙醇酸鈉或硫乙醇酸溶解于該溶液，如果需要可加入1mol/L氫氧化鈉溶液，以便在滅菌后該溶液呈pH值7.1±0.2。如需要過(guò)濾，再次加熱該溶液但不得煮沸，并趁熱以濕潤(rùn)濾紙將該溶液過(guò)濾。加入刃天青

14、鈉溶液，混勻，并將該培養(yǎng)基置于適當(dāng)容器中，該容器應(yīng)為培養(yǎng)基提供特定的面積/深度比，以使在培養(yǎng)期結(jié)束后能明確顯示氧氣攝入的變色部分不超過(guò)培養(yǎng)基的上半部分。使用經(jīng)過(guò)驗(yàn)證的工藝進(jìn)行滅菌。如果需要貯存該培養(yǎng)基，應(yīng)將其置于無(wú)菌、氣密容器中，在225貯藏。如果超過(guò)三分之一的培養(yǎng)基已經(jīng)呈粉紅色，可以用以下方法恢復(fù)該培養(yǎng)基功能，但每批培養(yǎng)基僅能恢復(fù)一次：在水浴鍋中或者自由流動(dòng)蒸汽中加熱該容器，直至粉色消失，并迅速放涼，須小心防止非無(wú)菌空氣進(jìn)入到容器中。滅菌后培養(yǎng)基存放時(shí)間超過(guò)驗(yàn)證期限時(shí)，不得使用。Fluid Thioglycollate Medium is to be incubated at 30°

15、; 35° . For products containing a mercurial preservative that cannot be tested by the membrane filtration method, Fluid Thioglycollate Medium incubated at 20° 25° may be used instead of SoybeanCasein Digest Medium provided that it has been validated as described in Growth Promotion Te

16、st of Aerobes, Anaerobes, andFungi. Where prescribed or justified and authorized, the following alternative thioglycollate medium might be used. Prepare a mixture having the same composition as that of the Fluid Thioglycollate Medium, but omitting the agar and the resazurin sodium solution. Steriliz

17、e as directed above. The pH after sterilization is 7.1 ± 0.2. Heat in a water bath prior to use and incubate at 30 35 under anaerobic conditions.硫乙醇酸鹽流體培養(yǎng)基應(yīng)在3035條件下進(jìn)行培養(yǎng)。含有汞制劑防腐劑的產(chǎn)品不能使用膜過(guò)濾方法檢測(cè)。經(jīng)需氣菌、厭氧菌、真菌促生長(zhǎng)試驗(yàn)驗(yàn)證，在2025培養(yǎng)時(shí)，大豆酪蛋白消化培養(yǎng)基可以替代硫乙醇酸鹽流體培養(yǎng)基。經(jīng)合理授權(quán)，配制的與硫乙醇酸鹽流體培養(yǎng)基成分相同，但省略了瓊脂和刃天青溶液的培養(yǎng)基，可以替代硫乙醇酸

18、鹽流體培養(yǎng)基使用。按上述方法滅菌，滅菌后pH值為pH：7.1±0.2。使用前用水浴加熱，置于3035厭氧條件下培養(yǎng)。pH after sterilization: 7.3±0.2.大豆-酪胨消化物培養(yǎng)基酪蛋白胰酶消化物17.0g大豆粉木瓜蛋白酶消化物3.0g氯化鈉5.0g磷酸氫二鉀2.5g水合葡萄糖/無(wú)水葡萄糖2.5/2.3純化水1000mL滅菌后pH：7.1±0.2Dissolve the solids in the Purified Water, heating slightly to effect a solution. Cool the solution

19、to room temperature, and adjust the pH with 1 N sodium hydroxide so that, after sterilization, it will have a pH of 7.3 ± 0.2. Filter, if necessary to clarify, dispense into suitable containers, and sterilize using a validated procedure. Store at a temperature between 2° and 25° in a

20、sterile well-closed container, unless it is intended for immediate use. Do not use the medium for a longer storage period than has been validated.將固體物質(zhì)置純化水中，輕微加熱使其溶解。溶液放涼至室溫，并用1mol/L氫氧化鈉溶液調(diào)整pH值，使其滅菌后pH值為7.1±0.2。如需要使之澄清，則過(guò)濾，分裝入適合的容器，并用經(jīng)過(guò)驗(yàn)證的程序滅菌。如果不立刻使用，則保存在225無(wú)菌且密閉良好的容器中。滅菌后培養(yǎng)基存放時(shí)間超過(guò)驗(yàn)證期限時(shí)，不得使用。S

21、oybeanCasein Digest Medium is to be incubated at 22.5° ± 2.5°.大豆-酪胨消化物培養(yǎng)基在22.5±2.5條件下培養(yǎng)。Media for Penicillins or Cephalosporins用于青霉素和頭孢菌素的培養(yǎng)基Where sterility test media are to be used in the Direct Inoculation of the Culture Medium method under Test for Sterility of the Product to

22、 be Examined, modify the preparation of Fluid Pancreatic Digest of Casein 17.0 g Papaic Digest of Soybean Meal 3.0 g Sodium Chloride 5.0 g Dibasic Potassium Phosphate 2.5 g Dextrose Monohydrate/Anhydrous 2.5/2.3 g Purified Water 1000 mL Thioglycollate Medium and the SoybeanCasein Digest Medium as fo

23、llows. To the containers of each medium, transfer aseptically a quantity of -lactamase sufficient to inactivate the amount of antibiotic in the specimen under test. Determine the quantity of -lactamase required to inactivate the antibiotic by using a -lactamase preparation that has been assayed prev

24、iously for itspenicillin- or cephalosporin-inactivating power. NOTESupplemented -lactamase media can also be used in the membrane filtration test. 當(dāng)無(wú)菌檢查培養(yǎng)基用于供試產(chǎn)品無(wú)菌檢查項(xiàng)下的直接接種法檢驗(yàn)時(shí)，按如下內(nèi)容變更硫乙醇酸鹽流體培養(yǎng)基和大豆-酪胨培養(yǎng)基的制備方法。向每一種培養(yǎng)基的容器中，以無(wú)菌操作轉(zhuǎn)移足夠量能滅活供試樣品中抗生素的-內(nèi)酰胺酶（之前已經(jīng)對(duì)-內(nèi)酰胺酶制品滅活青霉素或頭孢菌素的能力進(jìn)行過(guò)測(cè)定，據(jù)此來(lái)確定滅活抗生素所需的-內(nèi)酰胺酶量）

25、。（注：添加-內(nèi)酰胺酶的培養(yǎng)基也可以用于膜過(guò)濾試驗(yàn)）。Alternatively (in an area completely separate from that used for sterility testing), confirm that an appropriate amount of -lactamase is incorporated into the medium, following either method under Method Suitability Test, using less than 100 colony-forming units (cfu) of S

26、taphylococcus aureus (see Table 1) as the challenge. Typical microbial growth of the inoculated culture must be observed as a confirmation that the -lactamase concentration is appropriate. 或者（在與無(wú)菌試驗(yàn)完全隔離的區(qū)域），按照驗(yàn)證試驗(yàn)項(xiàng)下的任意一種方法，使用少于100cfu的金黃色葡萄球菌（表1）作為驗(yàn)證菌，來(lái)確認(rèn)該培養(yǎng)基中含有的-內(nèi)酰胺酶量是否適宜。必須觀測(cè)到接種后培養(yǎng)物中出現(xiàn)典型的微生物生長(zhǎng)，才能確認(rèn)

27、-內(nèi)酰胺酶量是適宜的。表1 用于促生長(zhǎng)試驗(yàn)和方法驗(yàn)證試驗(yàn)的測(cè)試菌株需氣菌金黃色葡萄球菌ATCC 6538, CIP 4.83, NCTC 10788, NCIMB 9518, NBRC13276枯草芽孢桿菌ATCC 6633, CIP 52.62, NCIMB 8054, NBRC 3134銅綠假單胞菌ATCC 9027, NCIMB 8626, CIP 82.118, NBRC 13275厭氧菌生孢梭菌ATCC 19404, CIP 79.3, NCTC 532 or ATCC 11437, NBRC14293真菌白色念珠菌ATCC 10231, IP 48.72, NCPF 3179, N

28、BRC 1594巴西曲霉ATCC 16404, IP 1431.83, IMI 149007, NBRC 9455替代微生物是藤黃微球菌。當(dāng)需要不形成芽孢微生物時(shí)，生孢梭菌的替代微生物是普通擬桿菌。The media used comply with the following tests, carried out before, or in parallel, with the test on the product to be examined.所使用的培養(yǎng)基須符合下列試驗(yàn)，這些試驗(yàn)應(yīng)在供試產(chǎn)品檢驗(yàn)前完成或者同時(shí)進(jìn)行。Sterility培養(yǎng)基無(wú)菌性Incubate portions of

29、the media for 14 days. No growth of microorganisms occurs.取部分檢驗(yàn)用培養(yǎng)基，連續(xù)培養(yǎng)14天，應(yīng)不得出現(xiàn)微生物生長(zhǎng)。Growth Promotion Test of Aerobes, Anaerobes, and Fungi需氣菌、厭氧菌和真菌的促生長(zhǎng)試驗(yàn)Test each lot of ready-prepared medium and each batch of medium prepared either from dehydrated medium or from ingredients. Suitable strains of

30、 microorganisms are indicated in Table 1.每一批配制好的培養(yǎng)基（采用脫水培養(yǎng)基或按配方制備的培養(yǎng)基）均需進(jìn)行檢查，使用的微生物菌株見表1。Inoculate portions of Fluid Thioglycollate Medium with a small number (not more than 100 cfu) of the following microorganisms, using a separate portion of medium for each of the following species of microorganis

31、m: Clostridium sporogenes, Pseudomonas aeruginosa, and Staphylococcus aureus. Inoculate portions of alternative thioglycollate medium with a small number (not more than 100 cfu) of Clostridium sporogenes. Inoculate portions of SoybeanCasein Digest Medium with a small number (not more than 100 cfu) o

32、f the following microorganisms, using a separate portion of medium for each of the following species of microorganism: Aspergillus brasiliensis, Bacillus subtilis, and Candida albicans. Incubate for not more than 3 days in the case of bacteria and not more than 5 days in the case of fungi. Seed lot

33、culture maintenance techniques (seed-lot systems) are used so that the viable microorganisms used for inoculation are not more than five passages removed from the original master seed-lot.去取部分硫乙醇酸鹽流體培養(yǎng)基，接種少量（不超過(guò)100cfu）下列微生物，每一種微生物均分別接種于單獨(dú)培養(yǎng)基中：生孢梭菌、銅綠假單胞菌、金黃色葡萄球菌（在替代硫乙醇酸鹽的流體培養(yǎng)基中接種少量（不超過(guò)100cfu）生孢梭菌）。在

34、大豆-酪胨消化物培養(yǎng)基中接種少量（不超過(guò)100cfu）下列微生物，每一種微生物均接種于單獨(dú)的培養(yǎng)基：黑曲霉、枯草芽孢桿菌、白色念珠菌。細(xì)菌培養(yǎng)時(shí)間不超過(guò)3天，真菌培養(yǎng)時(shí)間不超過(guò)5天。采用適宜的菌種保藏技術(shù)，以確保用于接種的微生物的傳代次數(shù)不超過(guò)5代。The media are suitable if a clearly visible growth of the microorganisms occurs.如果可見清晰的微生物生長(zhǎng)，則該培養(yǎng)基是符合要求的。DILUTING AND RINSING FLUIDS FOR MEMBRANE FILTRATION用于膜過(guò)濾的稀釋劑和沖洗液Fluid

35、A稀釋劑APREPARATION制備Dissolve 1 g of peptic digest of animal tissue in water to make 1 L, filter or centrifuge to clarify, if necessary, and adjust to a pH of 7.1 ± 0.2. Dispense into containers, and sterilize using a validated process.將1g動(dòng)物組織胃蛋白酶消化物溶于1L水中，如果需要?jiǎng)t通過(guò)過(guò)濾或離心使其澄清，再調(diào)節(jié)pH值至7.1±0.2。分裝入容

36、器中，并用經(jīng)過(guò)驗(yàn)證的工藝滅菌。PREPARATION FOR PENICILLINS OR CEPHALOSPORINS用于青霉素或頭孢菌素的稀釋劑制備Aseptically add to the above Preparation, if necessary, a quantity of sterile -lactamase sufficient to inactivate any residual antibiotic activity on the membranes after the solution of the test specimen has been filtered (s

37、ee Media for Penicillins or Cephalosporins).在供試樣品溶液已經(jīng)過(guò)濾之后，如果需要，向上述制備的稀釋劑中，以無(wú)菌操作加入數(shù)量足夠滅活濾膜上殘余抗生素的-內(nèi)酰胺酶（見用于青霉素或頭孢菌素的培養(yǎng)基）。Fluid D稀釋劑DTo each L of Fluid A add 1 mL of polysorbate 80, adjust to a pH of 7.1 ± 0.2, dispense into containers, and sterilize using a validated process. Use this fluid for a

38、rticles containing lecithin or oil, or for devices labeled as “sterilepathway.”向每升稀釋劑A中，加入1mL聚山梨酯80，調(diào)節(jié)pH值至7.1±0.2，分裝入容器中，并使用經(jīng)過(guò)驗(yàn)證的工藝滅菌。此液體用于含有卵磷脂或油脂的樣品，或用于標(biāo)為“無(wú)菌通道”的器械。Fluid K稀釋劑KDissolve 5.0 g of peptic digest of animal tissue, 3.0 g of beef extract, and 10.0 g of polysorbate 80 in water to make

39、 1 L. Adjust the pH to obtain, after sterilization, a pH of 6.9 ± 0.2. Dispense into containers, and sterilize using a validated process.將5.0g動(dòng)物組織胃蛋白酶消化物、3.0牛肉提取物、10.0g聚山梨酯80溶解于1L水中。調(diào)節(jié)pH值，使其滅菌后pH值為6.9±0.2。分裝入容器中，并使用經(jīng)過(guò)驗(yàn)證的工藝滅菌。METHOD SUITABILITY TEST方法適用性試驗(yàn)Carry out a test as described below

40、 under Test for Sterility of the Product to be Examined using exactly the same methods, except for the following modifications.嚴(yán)格按照供試產(chǎn)品無(wú)菌檢查項(xiàng)下的方法進(jìn)行無(wú)菌檢查。當(dāng)使用到以下方法并需要進(jìn)行方法調(diào)整時(shí)，需重新進(jìn)行方法適用性實(shí)驗(yàn)。Membrane Filtration膜過(guò)濾法After transferring the content of the container or containers to be tested to the membrane, ad

41、d an inoculum of a small number of viable microorganisms (not more than 100 cfu) to the final portion of sterile diluent used to rinse the filter.在將一個(gè)或多個(gè)供試容器中的內(nèi)容物轉(zhuǎn)移到濾膜之后，在最后一次的沖洗液中加入少量（不超過(guò)100cfu）測(cè)試菌株。Direct Inoculation直接接種法After transferring the contents of the container or containers to be tested (

42、for catgut and other surgical sutures for veterinary use: strands) to the culture medium, add an inoculum of a small number of viable microorganisms (not more than 100 cfu) to the medium.在將一個(gè)或多個(gè)供試容器（對(duì)于獸醫(yī)用的腸線和其他外科縫合用線：若干股線）中的內(nèi)容物轉(zhuǎn)移至培養(yǎng)基之后，將少量試驗(yàn)菌（不超過(guò)100cfu）加入培養(yǎng)基中。In both cases use the same microorganism

43、s as those described above under Growth Promotion Test of Aerobes, Anaerobes, and Fungi. Perform a growth promotion test as a positive control. Incubate all the containers containing medium for not more than 5 days.以上兩種情況，均使用上述需氣菌、厭氧菌、真菌促生長(zhǎng)試驗(yàn)項(xiàng)下規(guī)定的菌株。同時(shí)設(shè)置促生長(zhǎng)試驗(yàn)作為陽(yáng)性對(duì)照。微生物在相應(yīng)培養(yǎng)基中的培養(yǎng)時(shí)間不超過(guò)5天。If clearly vi

44、sible growth of microorganisms is obtained after the incubation, visually comparable to that in the control vessel without product, either the product possesses no antimicrobial activity under the conditions of the test or such activity has been satisfactorily eliminated. The test for sterility may

45、then be carried out without further modification.若培養(yǎng)后可見清晰的微生物生長(zhǎng)，外觀與未接種樣品的對(duì)照菌生長(zhǎng)類似，則認(rèn)為該產(chǎn)品在此試驗(yàn)條件下沒有抑菌作用，或者認(rèn)為可能存在的抑菌作用已經(jīng)被較完全的消除。此時(shí)可以認(rèn)為該方法無(wú)需進(jìn)一步的變更，無(wú)菌試驗(yàn)依法檢查即可。If clearly visible growth is not obtained in the presence of the product to be tested, visually comparable to that in the control vessels without p

46、roduct, the product possesses antimicrobial activity that has not been satisfactorily eliminated under the conditions of the test. Modify the conditions in order to eliminate the antimicrobial activity, and repeat the Method Suitability Test.與未接種樣品的對(duì)照相比，若在供試品存在條件下不能觀察到肉眼可見的混濁，則認(rèn)為該試驗(yàn)條件下不能消除供試品的抑菌作用。需

47、要對(duì)實(shí)驗(yàn)條件進(jìn)行調(diào)整以消除抗菌活性，并重新進(jìn)行方法適用性試驗(yàn)。This method suitability is performed (a) when the test for sterility has to be carried out on a new product; and (b) whenever there is a change in the experimental conditions of the test. The method suitability may be performed simultaneously with the Test for Sterilit

48、y of the Product to be Examined.當(dāng)一個(gè)新產(chǎn)品進(jìn)行無(wú)菌試驗(yàn)時(shí)和無(wú)論何時(shí)無(wú)菌試驗(yàn)的試驗(yàn)條件發(fā)生改變時(shí)，則需進(jìn)行此驗(yàn)證試驗(yàn)。該驗(yàn)證可以與供試產(chǎn)品無(wú)菌檢查同時(shí)進(jìn)行。TEST FOR STERILITY OF THE PRODUCT TO BE EXAMINED供試產(chǎn)品無(wú)菌檢查Number of Articles to Be Tested供試品數(shù)量Unless otherwise specified elsewhere in this chapter or in the individual monograph, test the number of articles s

49、pecified in Table 3. If the contents of each article are of sufficient quantity (see Table 2), they may be divided so that equal appropriate portions are added to each of the specified media. NOTEPerform sterility testing employing two or more of the specified media. If each article does not contain

50、 sufficient quantities for each medium, use twice the number of articles indicated in Table 3.除非在本章節(jié)的其他部分或在具體的各論中另有規(guī)定，供試物品的數(shù)量遵照表3中的規(guī)定。如果每個(gè)被檢驗(yàn)物品的內(nèi)容物有足夠數(shù)量（見表2），可以將其分成若干等份，將適當(dāng)?shù)牡确菁尤氲矫總€(gè)指定的培養(yǎng)基。（注：使用兩個(gè)或更多指定培養(yǎng)基，來(lái)進(jìn)行無(wú)菌試驗(yàn)。）如果每個(gè)被檢驗(yàn)物品的內(nèi)容物規(guī)格不能滿足單個(gè)培養(yǎng)基的接種量要求時(shí)，檢驗(yàn)量擴(kuò)大為表3所規(guī)定的檢驗(yàn)數(shù)量的2倍。表2 每種培養(yǎng)基的最少接種量供試品裝量最少接種量（除另有規(guī)定和授權(quán)）液體

51、少于1mL每個(gè)包裝全量140mL每個(gè)包裝半量，且不少于1mL大于40mL，但不大于100mL20mL大于100mL每個(gè)包裝內(nèi)容物的10%，但不得少于20mL液體抗生素1mL需懸浮或乳化的不溶性制劑、乳膏、油膏每個(gè)包裝不少于200mg內(nèi)容物固體少于50mg每個(gè)包裝全量50mg或以上，但不大于300mg每個(gè)包裝半量，但不少于50mg300mg5g150mg多余5g500mg獸醫(yī)用腸線和其他外科縫合線一股線的3部分（每個(gè)30cm長(zhǎng)）外科敷料/棉花/紗布（在包裝中）每包裝100mg縫合線和其他獨(dú)立包裝的一次性材料材料整體其他醫(yī)用設(shè)備整個(gè)設(shè)備，切成片或拆開表3批出廠產(chǎn)品的最小檢驗(yàn)數(shù)量批產(chǎn)品數(shù)量最小樣品數(shù)

52、量（除另有規(guī)定和授權(quán)）注射劑不多于100個(gè)容器10%或4個(gè)容器，選較多者多于100個(gè)，但不多于500個(gè)容器10個(gè)容器多于500個(gè)容器2%或者20個(gè)容器，選較少者大體積注射劑2%或者10個(gè)容器，選較少者固體抗生素固體制劑（<5g）20個(gè)容器固體制劑（5g）6個(gè)容器散裝固體見固體原料眼科和其他非注射劑不多于200個(gè)容器5%或者2個(gè)容器，選較多者多于200個(gè)容器10個(gè)容器如果該產(chǎn)品存在于單劑量容器中，應(yīng)用上述用于注射用劑方案獸醫(yī)用腸線和其他外科縫合線2%或5個(gè)包裝，選較多者，最多可達(dá)20個(gè)包裝不多于100件10%或4個(gè)物品，選較多者多于100但不超過(guò)500件10個(gè)物品多于500件2%或20個(gè)物

53、品，選較少者固體原料最多4個(gè)容器每個(gè)容器多于4個(gè)容器，但不多于50個(gè)容器20%或4個(gè)容器，選較多者超過(guò)50個(gè)容器2%或者10個(gè)容器，選較多者如果批量大小未知，請(qǐng)使用相關(guān)規(guī)定的最大數(shù)。如果一個(gè)容器的內(nèi)容物足夠接種2個(gè)培養(yǎng)基，則此表格給出的容器數(shù)量為用于全部2個(gè)培養(yǎng)基的數(shù)量。The test may be carried out using the technique of Membrane Filtration or by Direct Inoculation of the Culture Medium with the product to be examined. Appropriate n

54、egative controls are included. The technique of membrane filtration is used whenever the nature of the product permits; that is, for filterable aqueous preparations, for alcoholic or oily preparations, and for preparations miscible with, or soluble in, aqueous or oily solvents, provided these solven

55、ts do not have an antimicrobial effect in the conditions of the test.無(wú)菌檢驗(yàn)可以使用膜過(guò)濾法或培養(yǎng)基直接接種法進(jìn)行，應(yīng)設(shè)置適宜的陰性對(duì)照。但只要該產(chǎn)品的性質(zhì)許可，就應(yīng)使用膜過(guò)濾法，也就是說(shuō)，對(duì)水溶性制劑、酒精或油性制劑、易混合或溶解于水或油性溶劑的制劑，即使沒有抑菌作用，也均應(yīng)盡量采用薄膜過(guò)濾法進(jìn)行無(wú)菌檢查。Membrane Filtration膜過(guò)濾法Use membrane filters having a nominal pore size not greater than 0.45 m, in which the e

56、ffectiveness to retain microorganisms has been established. Cellulose nitrate filters, for example, are used for aqueous, oily, and weakly alcoholic solutions; and cellulose acetate filters, for example, are used for strongly alcoholic solutions. Specially adapted filters may be needed forcertain pr

57、oducts (e.g., for antibiotics).使用標(biāo)稱孔徑不大于0.45m的膜過(guò)濾器，此孔徑已知能夠有效截留微生物。例如，硝酸纖維素過(guò)濾器可用于水、油、烯醇溶液；而醋酸纖維素可用于濃醇溶液。特定產(chǎn)品（例如抗生素）可能需要特別改造過(guò)的特殊過(guò)濾器。The technique described below assumes that membranes about 50 mm in diameter will be used. If filters of a different diameter are used, the volumes of the dilutions and t

58、he washings should be adjusted accordingly. The filtration apparatus and membrane are sterilized by appropriate means. The apparatus is designed so that the solution to be examined can be introduced and filteredunder aseptic conditions: it permits the aseptic removal of the membrane for transfer to the medium, or it is suitable for carrying out the incubation after adding the medium to the apparatus itself.以下涉及的方法中所使用的均為直徑約50mm的濾膜。如果使用不同直徑的過(guò)濾器，稀釋液和沖洗液的體積應(yīng)當(dāng)做相應(yīng)調(diào)節(jié)。過(guò)濾器和濾膜都應(yīng)該經(jīng)過(guò)滅菌處理。過(guò)濾器應(yīng)該滿足